Natural-cell-mediated cytotoxicity against K-562 erythroleukemic cells and human papillomavirus (HPV)-16 harboring Sk-v keratinocytes was tested in 38 age- and sex-matched healthy volunteers and in patients with HPV-induced benign and malignant anogenital lesions: 9 persons with HPV-16-induced bowenoid papulosis (BP), 8 with anogenital carcinomas (5 with HPV-16- or 33-associated squamous-cell carcinomas of Bowen's type and 3 with HPV-6-associated Buschke-Loewenstein verrucous carcinomas) and 12 with HPV-6-induced condylomata acuminata. Both K-562 and Sk-v cells were killed by a non-adherent CD16+ subset of PBMC as revealed by cell fractionation on the basis of their adherence to plastic and by treatment with Leu-IIb monoclonal antibody (MAb) and complement. "Cold" target competitive assays demonstrated that both cell types inhibited lysis of labelled Sk-v cells. In patients with BP and anogenital carcinomas induced by HPV-16 or 33, there was a significant (at least at p less than 0.01) decrease of Sk-v cell lysis as compared with the healthy control group. Anti-K-562 activity was not affected. In patients with anogenital carcinomas the degree of Sk-v lysis was decreased in proportion to the duration of lesions (correlation coefficient-r = -0.79). Neither anti-K-562 nor anti-Sk-v cytotoxicities were significantly affected in patients with condylomata and with HPV-6 associated verrucous carcinomas. Short-term (3 hr) pre-incubation of normal PBMC with sera from patients with BP and HPV-16-associated anogenital carcinomas resulted in significant inhibition of their ability to lyse Sk-v cells. Lysis of K-562 cells remained unaffected. In patients with carcinomas, the suppressive effect of sera was associated with a lowering of the ability of their PBMC to lyse Sk-v cells (r = -0.79). In patients with longer tumor persistence, the suppressive effect of serum was proportionally higher (r = 0.86).